Glaucoma is a blinding eye disease in which damage to the optic nerve is accentuated by elevated intraocular pressure (IOP). In primary open angle glaucoma (POAG) and a number of secondary glaucomas, there appears to be an obstruction of the outflow pathway involving a decrease in the ability of aqueous humor to pass through the trabecular meshwork and into Schlemm's canal. Over the past three years I have been doing fellowship research on mediator responses and oxidative stress in human trabecular meshwork (HTM) cells which could possibly provide clues to observed changes in the outflow pathway. My recent findings have shown only modest elevations of H2O2 (if they are sustained) produce both "homeostatic" and potentially pathogenic changes in HTM cells which could be relevant to glaucoma pathogenesis and treatment. More details concerning responses of the HTM cell type to potentially damaging environmental influences due to H2O2, lipid hydroperoxides, and other forms of oxidative stress are only now being characterized. Cellular properties which are being characterized include growth potential phagocytosis, and other HTM cell functions. For both acute and chronic exposure to H2O2 and other potential sources of oxidative stress, some of the newer molecular biology/biochemistry approaches are also being used to evaluate the responses of the HTM cells. Such studies are helping to define the sequential and dose related patterns of HTM stress responses and have already provided specific information regarding the effect of oxidative stress on growth factors and their receptors in the HTM cells. These investigations should help to provide an improved understanding of HTM cell responses relevant to alterations which may contribute to outflow obstruction and elevated IOP. Studies of the ability of these cells to withstand injury and different types of oxidative stress could provide valuable clues to understanding pathogenic mechanisms of POAG.